This case had typical features of an
adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition. “
“M. Nakamura, H. Ito, Y. Nakamura, R. Wate, S. Kaneko, S. Nakano, S. Matsumoto and H. Kusaka (2011) Neuropathology and Applied Neurobiology37, 307–314 Smad ubiquitination regulatory factor-2 in progressive supranuclear palsy Aims: Smad ubiquitination regulatory factor-2 (Smurf2) is an E3 ligase that belongs to the HECT domain ubiquitin ligase family. Smurf2 can interact Lapatinib concentration with Smad
proteins and promote their ubiquitin-dependent degradation, thereby controlling the cellular levels of these signalling mediators. Phosphorylated Smad2/3 (pSmad2/3) was recently identified in phosphorylated tau (phospho-tau) inclusions in patients with progressive supranuclear palsy (PSP). As Smurf2 is the E3 ligase of pSmad2, we aimed at investigating the relationship selleck products among Smurf2, pSmad2/3 and phospho-tau in this study. Methods: The brains of six PSP and three control patients without neurological disorder were investigated by immunohistochemical analysis. Results: In the control subjects, Smurf2 immunoreactivity was not demonstrable in the neurones and glial cells, and that for pSmad2/3 was observed exclusively in neuronal and Urease glial nuclei. In PSP patients, the pathognomonic neuronal and glial
phospho-tau inclusions were immunopositive for both Smurf2 and pSmad2/3. The intensity of pSmad2/3 immunosignals of neuronal and glial nuclei containing phospho-tau inclusions was less than that for the cells without the inclusions. Triple immunofluorescence staining for Smurf2, pSmad2/3 and phospho-tau revealed co-localization of these proteins within the neuronal and glial inclusions; and in some globose neurofibrillary tangles, the Smurf2 immunoreactivity appeared more centrally distributed than that of pSmad2/3 and phospho-tau. Conclusions: This is the first demonstration of the presence of Smurf2 immunoreactivity in the phospho-tau inclusions in PSP. These findings suggest that Smurf2 plays a significant role in the pathomechanism of PSP by causing abnormal redistribution of neuronal nuclear pSmad2/3 to the cytoplasm. “
“von Economo neurones (VEN) are bipolar neurones located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI), areas affected early in behavioural variant frontotemporal dementia (bvFTD), in which VEN may constitute a selectively vulnerable cellular population. A previous study has shown a selective loss of VEN in FTD above other neurones in the ACC of FTD.